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Biomatériaux pour application chirurgicale : élaboration et fonctionnalisation pour une bioadhésion thermorégulée

Abstract : Pancreatic surgery, which leads to 5 % of mortality and around 50 % of morbidity, is one of the most critical digestive operations. The most serious complication is the appearance of pancreatic fistulas (PFs), i.e. enzymatic leaks from the surgical sutures to the peritoneal environment that can lead to the life threatening of the patient. To date, no medical device is indicated for the prevention of these FPs. The aim of this project is to design and validate a biomaterial constituted of a matrix that will ensure the dual function of absorbent and antibacterial agent reservoir, on which a chemical grafting should confer thermoregulated bioadhesive properties. The first part of this work is devoted to the optimisation of the absorbent matrix, based on alginate and chitosan, already developed during a previous thesis. Three types of drying processes were compared: drying by evaporation, lyophilisation and drying in supercritical CO2 medium. These different processes led to materials with different internal structures and porosities. The impact of these structures was evaluated in terms of swelling capacity in various media, including a simulated pancreatic environment, but also in terms of enzymatic resistance and release of an active molecule. Taking into account the obtained results, drying by evaporation was identified as the most appropriate process. In a second part, poly (N-isopropylacrylamide) (PNIPAM) was synthesised by controlled polymerisation (RAFT) in order to be grafted onto the absorbent matrix surfaces. PNIPAM is a thermosensitive polymer with bioadhesive properties which depend on the temperature. This polymer is usually bioadhesive above its lower critical solution temperature (LCST), around 32 ° C. In this study, the molar mass and the grafting density of PNIPAM are the two main parameters studied for the surface modifications. Finally, the surface properties of the grafted matrices were characterised. In vitro, the materials showed thermosensitive bioadhesive properties, with a cellular bioadhesion mainly observed above the LCST. However, ex vivo tests exhibited higher bioadhesion on porcine organs at lower temperatures. This study led to the development of absorbent biomaterials with thermoregulated surface properties. Further understanding of the relationship between surface properties and in vivo bioadhesion would allow the optimisation of the thermoregulated surface properties.
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Guillaume Conzatti. Biomatériaux pour application chirurgicale : élaboration et fonctionnalisation pour une bioadhésion thermorégulée. Médecine humaine et pathologie. Université Paul Sabatier - Toulouse III, 2017. Français. ⟨NNT : 2017TOU30159⟩. ⟨tel-01938955⟩

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